The research detailed in this application proposes continued investigations into the regulation of two important "branch point" enzymes, glutamine synthetase and PRPP synthetase, in normal and neoplastic tissues and in cells in culture. The experiments seek information on the in vitro and in vivo enzyme regulation, the role of glutamine in this regulation, whether "induction" of enzyme activity is paralleled by similar changes in the cellular transport of glutamine, and whether the regulation observed differs in normal and neoplastic cells. Mitogen-stimulated lymphocytes will also be used to study the interaction of the marked increase in de novo purine biosynthesis that occurs after mitogen stimulation with the regulation of the activity of these enzymes important for de novo purine biosynthesis. The research will continue experiments investigating the interaction of enzymes with cell membranes. These experiments will further characterize the interaction of human erythrocyte AMP deaminase with the inner surface of the human erythrocyte membrane, seek the relationship of specific membrane proteins with AMP deaminase, seek whether other enzymes bind at the same locus on the membrane, and seek how the interaction of AMP deaminse and the cell membrane influences enzyme catalytic activity. The investigations therefore continue the central laboratory interest in purine metabolism and have the specific goal of providing models to detail mechanisms of cell regulation and cell growth, particularly as directed toward the regulation of enzyme activities and steady state levels in normal tissues and how such regulation is modified in the cancer cell.